DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on May 26, 2026 has been entered.
Status of the Claims
Claims 1-36 were originally filed January 17, 2020.
The amendment received May 26, 2020 amended claims 3-9, 12, 14, 16-18, 20, 21, 24, 29-32, and 35 and canceled claims 10, 13, 15, 19, 22, 23, 33, and 34.
The amendment received December 1, 2023 amended claims 1 and 7-9.
The amendment received June 13, 2024 amended claims 1, 2, 4-9, 11, 12, 14, 16-18, 20, and 21; cancelled claim 3; and added new claim 37.
The amendment received February 25, 2025 amended claims 1, 8, 9, and 37. Please note: several claims have the incorrect status identifier.
The amendment received January 15, 2026 amended claims 1, 6, 11, 14, and 29 and cancelled claim 7.
The amendment received May 26, 2026 amended claims 1, 8, and 9.
Claims 1, 2, 4-6, 8, 9, 11, 12, 14, 16-18, 20, 21, 24-32, and 35-37 are currently pending.
Claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 are currently under consideration.
Election/Restrictions
Applicants elected, without traverse, Group I (claims 1-9, 11, 12, 14, 16-18, 20, 21, and 24-30) in the reply filed on December 1, 2023. Claims 31, 32, 35, and 36 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method, there being no allowable generic or linking claim.
Applicants elected, without traverse, SEQ ID NO: 1, a B cell epitope and a T cell epitope, PEG-3000, SEQ ID NO: 4, and a supermolecular complex as the species in the reply filed on December 1, 2023. Claims 4, 7, 14, and 25-30 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected species, there being no allowable generic or linking claim.
Please note: applicants elected subgenuses for several of the species, therefore, the subgenuses were searched. In addition, if the particulars of the species or subgenuses could not be readily ascertained from the specification, the claims directed to the nonelected species or subgenuses were withdrawn (e.g. SEQ ID NO: 1 forms b-sheets therefore, the claim to the alpha helix was withdrawn; applicants did not supply the chemical formula for PEG-3000 and the formulas was not recited in the specification so claim 14 was withdrawn, etc.).
Please note: regarding the arguments made in the response received June 13, 2024, see the following:
The election of a B cell epitope and a T cell epitope did not refer to any length limit, therefore, claim 7 was withdrawn. A species does not necessarily fall within a genus. In addition, applicants were instructed to elect a single, specific species.
Applicants should provide the structure of PEG-3000 if they wish for a claim to be considered (i.e. claim 14). Please note: applicants may NOT make a different election (see page 6, claim 14 section).
Again, regarding claims 25-30, an election of a genus (i.e. supermolecular complex) does not necessarily encompass a species. In addition, applicants were instructed to elect a single, specific species.
Regarding claims 20, 21, and new claim 37, applicants may not alter an election by original presentation during prosecution. If applicants did not understand the election requirement, applicants should have called the examiner of record for clarification.
Applicants elected, with traverse, a conjugate that elicits a T cell response in the reply filed on December 1, 2023. The traversal is on the grounds that a serious search burden does not exist. This is not found persuasive because the present is a 371 (National Stage), therefore, the art of record utilized to break Unity of Invention should be argued. Furthermore, applicants were not limited to electing a species of T cell response or antibody response just as applicants were not limited to elect a T cell epitope or a B cell antigen for species B. The requirement is still deemed proper and is therefore made FINAL. Claims 20 and 37 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on December 1, 2023.
The election of species has been made FINAL. Applicants should NOT continue to traverse the species particularly since the original election of species was made WITHOUT traverse (for the majority of the species elections).
Priority
The present application is a 371 (National Stage) of PCT/US2018/042762 filed July 18, 2018 which claims the benefit of 62/533,910 filed July 18, 2017.
Sequence Interpretation
The Office interprets claims comprising SEQ ID NOs: in the following manner: “comprising a sequence of SEQ ID NO: 1” requires only a 2mer of SEQ ID NO: 1, “comprising the sequence of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 with any N-/C-terminal additions or any 5’/3’ additions, “consisting of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 and the same length as SEQ ID NO: 1, and “selected from the group consisting of SEQ ID NOs: 1, 2, and 3” requires the full-length sequence with 100% identity to SEQ ID NOs: 1, 2, or 3 and the same length as SEQ ID NOs: 1, 2, or 3.
Withdrawn Rejections
The rejection of claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement (new matter) is withdrawn in view of the amendment received May 26, 2026.
The rejection of claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent 12,290,603 (previously copending Application No. 17/764,406) is withdrawn in view of the TD filed May 26, 2026 and approved May 29, 2026.
The rejection of claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 7, 9, 11, 12, 14, 17-21, 23, 24, 32, 36, and 39 of claims 1-20 of U.S. Patent 12,290,603 (previously copending Application No. 17/608,443) in view of Ingber et al. U.S. Patent Application Publication 2015/0218252 published August 6, 2015 is withdrawn in view of the TD filed May 26, 2026 and approved May 29, 2026.
New Rejection
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention. One of skill in the art would not be able to determine the scope of the present claims. For example, it is unclear if other members are present in the Markush group or not since open comprising language is utilized.
See MPEP 2173.05(h). A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. See Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. If a Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group "comprising" or "consisting essentially of" the recited alternatives), the claim should generally be rejected under 35 USC 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim. See In re Kiely, 2022 USPQ2d 532 at 2* (Fed. Cir. 2022) (each independent claim recites "a selection from the group comprising a person, an animal, an animated character, a creature, an alien, a toy, a structure, a vegetable, and a fruit." … (emphasis added). "Given the breadth of variation among the specified alternatives and the use of the open-ended word ’comprising’ to define the scope of the list, we affirm the Board's conclusion that the pending claims recite improper Markush language and are indefinite under § 112(b).").
Maintained Rejections and/or Modified* Rejections
*wherein the modification is due to amendment
Claim Rejections - 35 USC § 112
Claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of SEQ ID NOs: 1, 2, 23, 24, 25, 26, 27, 28, 29, 30, 34, 35, 36, 37, 52, 53, 54, 55, 56, 57, 58, 59, 60, 62, 63, and 64 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: SEQ ID NOs: 1, 2, 23, 24, 25, 26, 27, 28, 29, 30, 34, 35, 36, 37, 52, 53, 54, 55, 56, 57, 58, 59, 60, 62, 63, and 64 do not share a common core structure/domain/etc. and a common use. Please note: SEQ ID NOs: 1 and 2 share a common core structure; SEQ ID NOs: 23-25 share a common core structure; SEQ ID NOs: 27-29 share a common core structure; SEQ ID NOs: 35 and 36 share a common core structure; SEQ ID NOs: 52-56, 58, and 64 share a common core structure; SEQ ID NOs: 57, 59, and 60 share a common core structure. See Table 1 in the originally filed specification (pages 18-20).
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Arguments and Response
Applicants’ arguments directed to the rejection under improper Markush grouping of alternatives, for claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 were considered but are not persuasive for the following reasons.
Applicants contend that the SEQ ID NOs: in independent claim 1 are not a Markush group because the list of alternatives is not closed (MPEP § 2117 and § 2173.05(h)). Alternatively, applicants contend that all the SEQ ID NOs: share both a structural similarity and a common use.
Applicants arguments are not convincing because a list of alternatives is considered a Markush group. Applicants’ arguments are not convincing since the structural features of beta sheet and alpha helix are not a common use (i.e. forming beta sheets is one common use and forming alpha helixes is a separate common use). In addition, the Markush members must have BOTH a common use AND a single structural similarity. Many of the sequences that form beta sheets do not share a common core structure.
SEQ ID NOs: 1 and 2 share a common core structure; SEQ ID NOs: 23-25 share a common core structure; SEQ ID NOs: 27-29 share a common core structure; SEQ ID NOs: 35 and 36 share a common core structure; SEQ ID NOs: 52-56, 58, and 64 share a common core structure; SEQ ID NOs: 57, 59, and 60 share a common core structure. See Table 1 in the originally filed specification (pages 18-20).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Collier et al. U.S. Patent Application Publication 2012/0282292 published November 8, 2012 and Ingber et al. U.S. Patent Application Publication 2015/0218252 published August 6, 2015.
For present claims 1, 2, 5, 6, 8, 9, 11, 16-18, 21, and 24, Collier et al. teach fibrillar adjuvants comprising a self-assembled peptide QQKFQFQFEQQ (SEQ ID NO: 1; present SEQ ID NO: 1) which self-assembles into b sheets and nanofibers wherein the length is 0.25-100 mm and the width is about 15 nm with antigen/epitope conjugated to the N- or C-terminus including OVA which has both B cell and T cell epitopes and elicits a T cell response and utilizing linkers including Ser-Gly-Ser-Gly (present SEQ ID NO: 4) and pluralities of the above (please refer to the entire specification particularly the abstract; Figures 1, 2; paragraphs 6, 8-13, 15, 32-37, 39-48; Table 1; Examples; claims). Collier et al. also teach utilizing polyethylene glycol (PEG) as a carrier (please refer to the entire specification particularly paragraphs 61, 64).
Thus, Collier et al. teach peptide epitope-(self-assembling peptide) or (self-assembling peptide)-epitope.
However, while Collier et al. teach PEG as a carrier, Collier et al. do not specifically teach conjugation of PEG to the nanofibers.
For present claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24, Ingber et al. teach self-assembling peptides conjugated to PEG as linkers or to increase half-life in vivo and conjugation of antigens to self-assembling peptides (please refer to the entire specification particularly the abstract; paragraphs 3, 19, 22, 25-27, 45, 46, 50, 69, 70, 76, 77, 79, 112, 113, 132-134, 136, 174-176, 194, 196, 198).
Thus, Ingber et al. teach PEG-(self-assembling peptide) or (self-assembling peptide)-PEG with the addition of an antigen to the self-assembling peptide.
Regarding the MW of PEG, compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. See In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977); In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); and Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007).
The claims would have been obvious because a particular known technique (i.e. conjugation of PEG to self-assembling peptides to increase half-life in vivo; utilization of PEG as a linker in fusion polypeptides, etc.) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense” (e.g. PEGylation of peptides to increase in vivo half-life is a well-understood, routine, and conventional method in the art). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Collier et al. and Ingber et al. for claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 were considered but are not persuasive for the following reasons.
Applicants discuss how unexpected results elicit antibody responses when delivered sublingually (Examples; paragraphs 168, 176; Figure 5B). Applicants contend that Collier et al. and Ingber et al. do not teach a construct that includes both an antigen/epitope and PEG particularly since Ingber et al. do not teach both PEG and an antigen. Applicants argue the references individually.
[000168] The inclusion of an additional immune peptide epitope conjugated to Q11 along
with PEG could potentially disrupt or alter self-assembly. It was thought that adding PEG to
a Q11-peptide epitope could potentially disrupt or alter the self-assembly of Q11 or the
nanofiber. Furthermore, in a PEG-peptide design in which a cell adhesion motif was
contained within the fibrillizing domain, the adhesion motif was suggested to be buried within
the nanofiber core. We thus designed our material with the model peptide epitope OVA323-
339 connected via a flexible (Ser-Gly)₂ linker to the N-terminal of Q11, and a 3000 MW PEG
block on the C-terminal, postulating that this would create a Q11 peptide core with OVA
epitopes interspersed among the PEG corona. Due to the use of a polydisperse PEG block,
the resulting PEG-peptide conjugate (OVAQ11-PEG) was polydisperse (FIG. 11A, FIG.
11B).
Q11 is present SEQ ID NO: 5 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1) and SEQ ID NO: 6 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1-NHlinker-PEG).
Paragraph 168 suggests that the addition of PEG may alter SEQ ID NO: 5 without providing any data to support that claim. The scope of the peptide-polymer conjugate discussed in paragraph 168 is not the same as the present claims (e.g. unexpected results must be commensurate in scope with the present claims).
More importantly, paragraph 169 shows that SEQ ID NO: 6 with PEG self-assembles as expected and similar to SEQ ID NO: 5 without PEG.
[000176] Strikingly, sublingual immunization of mice with sheared OVAQ11-PEG + CT led to high titers of OVA-specific serum IgG, while sheared or unsheared OVAQ11 + CT failed to elicit stronger titers than pOVA + CT (FIG. 5B). Mice were immunized followed by boosts at
1 and 3 weeks after the primary immunization. The antibody response was extremely
durable, as even four months after the second boost, mice maintained high levels of antigen-
specific IgG in the serum. Furthermore, a recall response was observed after boosting mice
at week 20, suggesting that immune memory may have developed. To minimize the
potential confounding effects of mice swallowing material, we immunized deeply
anesthetized mice with a conservative volume of only 7 uL. To show that OVAQ11-PEG, and
not simply PEG conjugation, was necessary to promote the observed responses, we
immunized mice sublingually with pOVA-PEG + CT as a control, and observed no response
(FIG. 5A).
Q11 is present SEQ ID NO: 5 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1) and SEQ ID NO: 6 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1-NHlinker-PEG).
The scope of the peptide-polymer conjugate discussed in paragraph 176 is not the same as the present claims (e.g. unexpected results must be commensurate in scope with the present claims).
Furthermore, it is unclear why applicants feel that the antibody response results are surprising since SEQ ID NO: 6 folds as expected and similarly to SEQ ID NO: 5, PEGylation would increase serum half-life and extend plasma life, and utilization of an adjuvant would increase antibody response. Also see Figures 4B and 4C (no difference between OVAQ11 and OVAQ11-PEG). See Figure 5A. Regarding Figure 5B, the utilization of an adjuvant (cholera toxin/CT) would be expected to increase antibody response. Also see Figure 6A.
Applicants’ arguments are not convincing since the teachings of Collier et al. and Ingber et al. render the peptide-polymer conjugate of the instant claims prima facie obvious.
The present peptide-polymer conjugate has one of two structures:
peptide epitope-(self-assembling domain)-PEG or
PEG-(self-assembling domain)-peptide epitope.
Paragraph 11 of Ingber et al. teach a self-assembling peptide (i.e. isolated peptide – see paragraphs 6-10) can be conjugated to a ligand (i.e. PEG), a therapeutic agent (i.e. epitope), a binding molecule (i.e. epitope), and any combinations thereof.
Paragraph 19 of Ingber et al. teach the amino acid sequence (i.e. self-assembling peptide – see paragraphs 14-18) can be conjugated to a ligand including an antigen.
Paragraph 91 of Ingber et al. teach that the self-assembling peptide can be conjugated to one or more entities described herein (i.e. antigen, epitope, PEG) including a linker (PEG), a ligand (i.e. PEG, epitope), a therapeutic agent (i.e. epitope), a binding molecule (i.e. epitope), etc.
Paragraph 113 refers to PEG as a ligand.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Collier et al. teach a self-assembling peptides conjugated to antigens and PEG as a carrier but not specifically conjugated to a self-assembling peptide (see above). Ingber et al. teach self-assembling peptides conjugated to PEG (see above). PEG in both Collier et al. and Ingber et al. is utilized to increase half-life. The examiner of record would like to thank applicants for specifically pointing out that Ingber et al. also teach conjugation of self-assembling peptides to antigens (see paragraph 19).
The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." See In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) and In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989).
Claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Collier et al. U.S. Patent Application Publication 2014/0273148 published September 18, 2014 and Ingber et al. U.S. Patent Application Publication 2015/0218252 published August 6, 2015.
For present claims 1, 2, 5, 6, 8, 9, 11, 16-18, 21, and 24, Collier et al. teach fibrillar adjuvants comprising a self-assembled peptide QQKFQFQFEQQ (SEQ ID NO: 6; present SEQ ID NO: 1) which self-assembles into b sheets and nanofibers wherein the length is 1-100 mm and the size/length/diameter is 100 nm or less with B cell and/or T cell antigen/epitope conjugated to the N- or C-terminus and utilizing linkers including SGSG (present SEQ ID NO: 4) and pluralities of the above (please refer to the entire specification particularly the abstract; Figures 1, 4A, 4B, 8A; paragraphs 5-25, 29-32, 34-36, 56-58, 66-94, 100-102, 124, 125, 148-150, 153-155, 159, 171, 172; claims). Collier et al. also teach utilizing polyethylene glycol (PEG) as a carrier, cell delivery matrix, or as a tag for peptide purification (please refer to the entire specification particularly paragraphs 115, 119, 128, 144).
Thus, Collier et al. teach peptide epitope-(self-assembling peptide) or (self-assembling peptide)-epitope.
However, while Collier et al. teaches PEG as a carrier, Collier et al. do not specifically teach conjugation of PEG to the nanofibers.
For present claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24, Ingber et al. teach self-assembling peptides conjugated to PEG as linkers or to increase half-life in vivo and conjugation of self-assembling peptides to antigens (please refer to the entire specification particularly the abstract; paragraphs 3, 19, 22, 25-27, 45, 46, 50, 69, 70, 76, 77, 79, 112, 113, 132-134, 136, 174-176, 194, 196, 198).
Thus, Ingber et al. teach PEG-(self-assembling peptide) or (self-assembling peptide)-PEG with the addition of an antigen to the self-assembling peptide.
Regarding the MW of PEG, compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. See In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977); In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); and Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007).
The claims would have been obvious because a particular known technique (i.e. conjugation of PEG to self-assembling peptides to increase half-life in vivo; utilization of PEG as a linker in fusion polypeptides, etc.) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense” (e.g. PEGylation of peptides to increase in vivo half-life is a well-understood, routine, and conventional method in the art). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Collier et al. and Ingber et al. for claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 were considered but are not persuasive for the following reasons.
Applicants discuss how unexpected results elicit antibody responses when delivered sublingually (Examples; paragraphs 168, 176; Figure 5B). Applicants contend that Collier et al. and Ingber et al. do not teach a construct that includes both an antigen/epitope and PEG particularly since Ingber et al. do not teach both PEG and an antigen. Applicants argue the references individually.
Applicants’ arguments are not convincing since the teachings of Collier et al. and Ingber et al. render the peptide-polymer conjugate of the instant claims prima facie obvious.
[000168] The inclusion of an additional immune peptide epitope conjugated to Q11 along
with PEG could potentially disrupt or alter self-assembly. It was thought that adding PEG to
a Q11-peptide epitope could potentially disrupt or alter the self-assembly of Q11 or the
nanofiber. Furthermore, in a PEG-peptide design in which a cell adhesion motif was
contained within the fibrillizing domain, the adhesion motif was suggested to be buried within
the nanofiber core. We thus designed our material with the model peptide epitope OVA323-
339 connected via a flexible (Ser-Gly)₂ linker to the N-terminal of Q11, and a 3000 MW PEG
block on the C-terminal, postulating that this would create a Q11 peptide core with OVA
epitopes interspersed among the PEG corona. Due to the use of a polydisperse PEG block,
the resulting PEG-peptide conjugate (OVAQ11-PEG) was polydisperse (FIG. 11A, FIG.
11B).
Q11 is present SEQ ID NO: 5 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1) and SEQ ID NO: 6 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1-NHlinker-PEG).
Paragraph 168 suggests that the addition of PEG may alter SEQ ID NO: 5 without providing any data to support that claim. The scope of the peptide-polymer conjugate discussed in paragraph 168 is not the same as the present claims (e.g. unexpected results must be commensurate in scope with the present claims).
More importantly, paragraph 169 shows that SEQ ID NO: 6 with PEG self-assembles as expected and similar to SEQ ID NO: 5 without PEG.
[000176] Strikingly, sublingual immunization of mice with sheared OVAQ11-PEG + CT led to high titers of OVA-specific serum IgG, while sheared or unsheared OVAQ11 + CT failed to elicit stronger titers than pOVA + CT (FIG. 5B). Mice were immunized followed by boosts at
1 and 3 weeks after the primary immunization. The antibody response was extremely
durable, as even four months after the second boost, mice maintained high levels of antigen-
specific IgG in the serum. Furthermore, a recall response was observed after boosting mice
at week 20, suggesting that immune memory may have developed. To minimize the
potential confounding effects of mice swallowing material, we immunized deeply
anesthetized mice with a conservative volume of only 7 uL. To show that OVAQ11-PEG, and
not simply PEG conjugation, was necessary to promote the observed responses, we
immunized mice sublingually with pOVA-PEG + CT as a control, and observed no response
(FIG. 5A).
Q11 is present SEQ ID NO: 5 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1) and SEQ ID NO: 6 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1-NHlinker-PEG).
The scope of the peptide-polymer conjugate discussed in paragraph 176 is not the same as the present claims (e.g. unexpected results must be commensurate in scope with the present claims).
Furthermore, it is unclear why applicants feel that the antibody response results are surprising since SEQ ID NO: 6 folds as expected and similarly to SEQ ID NO: 5, PEGylation would increase serum half-life and extend plasma life, and utilization of an adjuvant would increase antibody response. Also see Figures 4B and 4C (no difference between OVAQ11 and OVAQ11-PEG). See Figure 5A. Regarding Figure 5B, the utilization of an adjuvant (cholera toxin/CT) would be expected to increase antibody response. Also see Figure 6A.
The present peptide-polymer conjugate has one of two structures:
peptide epitope-(self-assembling domain)-PEG or
PEG-(self-assembling domain)-peptide epitope.
Paragraph 11 of Ingber et al. teach a self-assembling peptide (i.e. isolated peptide – see paragraphs 6-10) can be conjugated to a ligand (i.e. PEG), a therapeutic agent (i.e. epitope), a binding molecule (i.e. epitope), and any combinations thereof.
Paragraph 19 of Ingber et al. teach the amino acid sequence (i.e. self-assembling peptide – see paragraphs 14-18) can be conjugated to a ligand including an antigen.
Paragraph 91 of Ingber et al. teach that the self-assembling peptide can be conjugated to one or more entities described herein (i.e. antigen, epitope, PEG) including a linker (PEG), a ligand (i.e. PEG, epitope), a therapeutic agent (i.e. epitope), a binding molecule (i.e. epitope), etc.
Paragraph 113 refers to PEG as a ligand.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Collier et al. teach a self-assembling peptides conjugated to antigens and PEG as a carrier but not specifically conjugated to a self-assembling peptide (see above). Ingber et al. teach self-assembling peptides conjugated to PEG (see above). PEG in both Collier et al. and Ingber et al. is utilized to increase half-life. The examiner of record would like to thank applicants for specifically pointing out that Ingber et al. also teach conjugation of self-assembling peptides to antigens (see paragraph 19).
The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." See In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) and In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989).
Claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 are rejected under 35 U.S.C. 103 as being unpatentable over Collier et al. U.S. Patent Application Publication 2016/0074509 published March 17, 2016 and Ingber et al. U.S. Patent Application Publication 2015/0218252 published August 6, 2015.
For present claims 1, 2, 5, 6, 8, 9, 11, 16-18, 21, and 24, Collier et al. teach fibrillar adjuvants comprising a self-assembled peptide QQKFQFQFEQQ (SEQ ID NO: 1; present SEQ ID NO: 1) which self-assembles into b sheets and nanofibers wherein the length is 0.01-100 mm with antigen/epitope conjugated to the N- or C-terminus including OVA which has both B cell and T cell epitopes and elicits a T cell response and utilizing linkers including SGSG (SEQ ID NO: 61; present SEQ ID NO: 4) and pluralities of the above (please refer to the entire specification particularly the abstract; Figures 1A, 1B, 2, 8A, 8B, 9A-9F; paragraphs 5, 7-15, 18, 45-53, 55-69, 95, 98, 99, 125-127, 130, 131; Table 1; Examples; claims). Collier et al. also teach utilizing polyethylene glycol (PEG) as a carrier and utilizing PEG to purify peptides (please refer to the entire specification particularly paragraphs 86, 121).
Thus, Collier et al. teach peptide epitope-(self-assembling peptide) or (self-assembling peptide)-epitope.
However, while Collier et al. teaches PEG as a carrier, Collier et al. do not specifically teach conjugation of PEG to the nanofibers.
For present claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24, Ingber et al. teach self-assembling peptides conjugated to PEG as linkers or to increase half-life in vivo and conjugations of self-assembling peptides to antigens (please refer to the entire specification particularly the abstract; paragraphs 3, 19, 22, 25-27, 45, 46, 50, 69, 70, 76, 77, 79, 112, 113, 132-134, 136, 174-176, 194, 196, 198).
Thus, Ingber et al. teach PEG-(self-assembling peptide) or (self-assembling peptide)-PEG with the addition of an antigen to the self-assembling peptide.
Regarding the MW of PEG, compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. See In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977); In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); and Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007).
The claims would have been obvious because a particular known technique (i.e. conjugation of PEG to self-assembling peptides to increase half-life in vivo; utilization of PEG as a linker in fusion polypeptides, etc.) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense” (e.g. PEGylation of peptides to increase in vivo half-life is a well-understood, routine, and conventional method in the art). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Collier et al. and Ingber et al. for claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 were considered but are not persuasive for the following reasons.
Applicants discuss how unexpected results elicit antibody responses when delivered sublingually (Examples; paragraphs 168, 176; Figure 5B). Applicants contend that Collier et al. and Ingber et al. do not teach a construct that includes both an antigen/epitope and PEG particularly since Ingber et al. do not teach both PEG and an antigen. Applicants argue the references individually.
Applicants’ arguments are not convincing since the teachings of Collier et al. and Ingber et al. render the peptide-polymer conjugate of the instant claims prima facie obvious.
[000168] The inclusion of an additional immune peptide epitope conjugated to Q11 along
with PEG could potentially disrupt or alter self-assembly. It was thought that adding PEG to
a Q11-peptide epitope could potentially disrupt or alter the self-assembly of Q11 or the
nanofiber. Furthermore, in a PEG-peptide design in which a cell adhesion motif was
contained within the fibrillizing domain, the adhesion motif was suggested to be buried within
the nanofiber core. We thus designed our material with the model peptide epitope OVA323-
339 connected via a flexible (Ser-Gly)₂ linker to the N-terminal of Q11, and a 3000 MW PEG
block on the C-terminal, postulating that this would create a Q11 peptide core with OVA
epitopes interspersed among the PEG corona. Due to the use of a polydisperse PEG block,
the resulting PEG-peptide conjugate (OVAQ11-PEG) was polydisperse (FIG. 11A, FIG.
11B).
Q11 is present SEQ ID NO: 5 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1) and SEQ ID NO: 6 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1-NHlinker-PEG).
Paragraph 168 suggests that the addition of PEG may alter SEQ ID NO: 5 without providing any data to support that claim. The scope of the peptide-polymer conjugate discussed in paragraph 168 is not the same as the present claims (e.g. unexpected results must be commensurate in scope with the present claims).
More importantly, paragraph 169 shows that SEQ ID NO: 6 with PEG self-assembles as expected and similar to SEQ ID NO: 5 without PEG.
[000176] Strikingly, sublingual immunization of mice with sheared OVAQ11-PEG + CT led to high titers of OVA-specific serum IgG, while sheared or unsheared OVAQ11 + CT failed to elicit stronger titers than pOVA + CT (FIG. 5B). Mice were immunized followed by boosts at
1 and 3 weeks after the primary immunization. The antibody response was extremely
durable, as even four months after the second boost, mice maintained high levels of antigen-
specific IgG in the serum. Furthermore, a recall response was observed after boosting mice
at week 20, suggesting that immune memory may have developed. To minimize the
potential confounding effects of mice swallowing material, we immunized deeply
anesthetized mice with a conservative volume of only 7 uL. To show that OVAQ11-PEG, and
not simply PEG conjugation, was necessary to promote the observed responses, we
immunized mice sublingually with pOVA-PEG + CT as a control, and observed no response
(FIG. 5A).
Q11 is present SEQ ID NO: 5 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1) and SEQ ID NO: 6 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1-NHlinker-PEG).
The scope of the peptide-polymer conjugate discussed in paragraph 176 is not the same as the present claims (e.g. unexpected results must be commensurate in scope with the present claims).
Furthermore, it is unclear why applicants feel that the antibody response results are surprising since SEQ ID NO: 6 folds as expected and similarly to SEQ ID NO: 5, PEGylation would increase serum half-life and extend plasma life, and utilization of an adjuvant would increase antibody response. Also see Figures 4B and 4C (no difference between OVAQ11 and OVAQ11-PEG). See Figure 5A. Regarding Figure 5B, the utilization of an adjuvant (cholera toxin/CT) would be expected to increase antibody response. Also see Figure 6A.
The present peptide-polymer conjugate has one of two structures:
peptide epitope-(self-assembling domain)-PEG or
PEG-(self-assembling domain)-peptide epitope.
Paragraph 11 of Ingber et al. teach a self-assembling peptide (i.e. isolated peptide – see paragraphs 6-10) can be conjugated to a ligand (i.e. PEG), a therapeutic agent (i.e. epitope), a binding molecule (i.e. epitope), and any combinations thereof.
Paragraph 19 of Ingber et al. teach the amino acid sequence (i.e. self-assembling peptide – see paragraphs 14-18) can be conjugated to a ligand including an antigen.
Paragraph 91 of Ingber et al. teach that the self-assembling peptide can be conjugated to one or more entities described herein (i.e. antigen, epitope, PEG) including a linker (PEG), a ligand (i.e. PEG, epitope), a therapeutic agent (i.e. epitope), a binding molecule (i.e. epitope), etc.
Paragraph 113 refers to PEG as a ligand.
In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Collier et al. teach a self-assembling peptides conjugated to antigens and PEG as a carrier but not specifically conjugated to a self-assembling peptide (see above). Ingber et al. teach self-assembling peptides conjugated to PEG (see above). PEG in both Collier et al. and Ingber et al. is utilized to increase half-life. The examiner of record would like to thank applicants for specifically pointing out that Ingber et al. also teach conjugation of self-assembling peptides to antigens (see paragraph 19).
The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." See In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) and In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,246,924 in view of Ingber et al. U.S. Patent Application Publication 2015/0218252 published August 6, 2015.
Both the present claims and the claims of U.S. Patent No. 11,246,924 are drawn to self-assembling peptides which form a nanofiber coupled to antigens.
Ingber et al. teach self-assembling peptides conjugated to PEG as linkers or to increase half-life in vivo (please refer to the entire specification particularly the abstract; paragraphs 3, 22, 25-27, 45, 46, 50, 69, 70, 76, 77, 79, 112, 113, 132-134, 136, 174-176, 194, 196, 198).
Thus, Ingber et al. teach PEG-(self-assembling peptide) or (self-assembling peptide)-PEG with the addition of an antigen to the self-assembling peptide.
Regarding the MW of PEG, compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. See In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977); In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978) (stereoisomers prima facie obvious); and Aventis Pharma Deutschland v. Lupin Ltd., 499 F.3d 1293, 84 USPQ2d 1197 (Fed. Cir. 2007).
The claims would have been obvious because a particular known technique (i.e. conjugation of PEG to self-assembling peptides to increase half-life in vivo; utilization of PEG as a linker in fusion polypeptides, etc.) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense” (e.g. PEGylation of peptides to increase in vivo half-life is a well-understood, routine, and conventional method in the art). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 11,246,924 in view of Ingber et al. for claims 1, 2, 5, 6, 8, 9, 11, 12, 16-18, 21, and 24 were considered but are not persuasive for the following reasons.
Applicants contend that Applicants discuss how unexpected results elicit antibody responses when delivered sublingually (Examples; paragraphs 168, 176; Figure 5B).
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 11,246,924 in view of Ingber et al. renders obvious the peptide-polymer conjugate of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
[000168] The inclusion of an additional immune peptide epitope conjugated to Q11 along
with PEG could potentially disrupt or alter self-assembly. It was thought that adding PEG to
a Q11-peptide epitope could potentially disrupt or alter the self-assembly of Q11 or the
nanofiber. Furthermore, in a PEG-peptide design in which a cell adhesion motif was
contained within the fibrillizing domain, the adhesion motif was suggested to be buried within
the nanofiber core. We thus designed our material with the model peptide epitope OVA323-
339 connected via a flexible (Ser-Gly)₂ linker to the N-terminal of Q11, and a 3000 MW PEG
block on the C-terminal, postulating that this would create a Q11 peptide core with OVA
epitopes interspersed among the PEG corona. Due to the use of a polydisperse PEG block,
the resulting PEG-peptide conjugate (OVAQ11-PEG) was polydisperse (FIG. 11A, FIG.
11B).
Q11 is present SEQ ID NO: 5 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1) and SEQ ID NO: 6 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1-NHlinker-PEG).
Paragraph 168 suggests that the addition of PEG may alter SEQ ID NO: 5 without providing any data to support that claim. The scope of the peptide-polymer conjugate discussed in paragraph 168 is not the same as the present claims (e.g. unexpected results must be commensurate in scope with the present claims).
More importantly, paragraph 169 shows that SEQ ID NO: 6 with PEG self-assembles as expected and similar to SEQ ID NO: 5 without PEG.
[000176] Strikingly, sublingual immunization of mice with sheared OVAQ11-PEG + CT led to high titers of OVA-specific serum IgG, while sheared or unsheared OVAQ11 + CT failed to elicit stronger titers than pOVA + CT (FIG. 5B). Mice were immunized followed by boosts at
1 and 3 weeks after the primary immunization. The antibody response was extremely
durable, as even four months after the second boost, mice maintained high levels of antigen-
specific IgG in the serum. Furthermore, a recall response was observed after boosting mice
at week 20, suggesting that immune memory may have developed. To minimize the
potential confounding effects of mice swallowing material, we immunized deeply
anesthetized mice with a conservative volume of only 7 uL. To show that OVAQ11-PEG, and
not simply PEG conjugation, was necessary to promote the observed responses, we
immunized mice sublingually with pOVA-PEG + CT as a control, and observed no response
(FIG. 5A).
Q11 is present SEQ ID NO: 5 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1) and SEQ ID NO: 6 (OVA323-339epitope-SGSGlinker-SEQ ID NO: 1-NHlinker-PEG).
The scope of the peptide-polymer conjugate discussed in paragraph 176 is not the same as the present claims (e.g. unexpected results must be commensurate in scope with the present claims).
Furthermore, it is unclear why applicants feel that the antibody response results are surprising since SEQ ID NO: 6 folds as expected and similarly to SEQ ID NO: 5, PEGylation would increase serum half-life and extend plasma life, and utilization of an adjuvant would increase antibody response. Also see Figures 4B and 4C (no difference between OVAQ11 and OVAQ11-PEG). See Figure 5A. Regarding Figure 5B, the utilization of an adjuvant (cholera toxin/CT) would be expected to increase antibody response. Also see Figure 6A.
The present peptide-polymer conjugate has one of two structures:
peptide epitope-(self-assembling domain)-PEG or
PEG-(self-assembling domain)-peptide epitope.
Paragraph 11 of Ingber et al. teach a self-assembling peptide (i.e. isolated peptide – see paragraphs 6-10) can be conjugated to a ligand (i.e. PEG), a therapeutic agent (i.e. epitope), a binding molecule (i.e. epitope), and any combinations thereof.
Paragraph 19 of Ingber et al. teach the amino acid sequence (i.e. self-assembling peptide – see paragraphs 14-18) can be conjugated to a ligand including an antigen.
Paragraph 91 of Ingber et al. teach that the self-assembling peptide can be conjugated to one or more entities described herein (i.e. antigen, epitope, PEG) including a linker (PEG), a ligand (i.e. PEG, epitope), a therapeutic agent (i.e. epitope), a binding molecule (i.e. epitope), etc.
Paragraph 113 refers to PEG as a ligand.
The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." See In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983) and In re Lemelson, 397 F.2d 1006, 1009, 158 USPQ 275, 277 (CCPA 1968)). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill in the art, including nonpreferred embodiments. See Merck & Co. v. Biocraft Labs., Inc. 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir. 1989), cert. denied, 493 U.S. 975 (1989).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
U.S. Patent Application Publication 2015/0031127
Shah et al., July 5, 2016, In vivo Evaluation of Site-specifically PEGylated Chemically Self-assembled Protein Nanostructures, Mol Pharm, 13(7): 2193-2203.
Future Communications
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/AMBER D STEELE/Primary Examiner, Art Unit 1658
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